Method and compositions for treating psoriasis

ABSTRACT

A topical composition useful for treating psoriasis and other skin disorders.

This application is a continuation of U.S. patent application Ser. No.16/156,820 filed Oct. 10, 2018 which is a continuation of U.S. patentapplication Ser. No. 15/639,886 filed Jun. 30, 2017, now U.S. Pat. No.10,124,013, which is a continuation of U.S. patent application Ser. No.13/655,161, filed Oct. 18, 2012, now U.S. Pat. No. 9,717,741, which is acontinuation of International Patent Application No. PCT/US12/59701,filed on Oct. 11, 2012, the contents of all are hereby incorporated byreference in their entireties into the present application.

TECHNICAL FIELD OF THE INVENTION

The present invention relates to a method and compositions for treatingpsoriasis and other similar skin disorders such as eczema, sunburn, andwound and scar care. The method comprises the topical administration ofa composition comprising a sterol ester.

BACKGROUND OF THE INVENTION

Psoriasis is a skin disease that results when skin cells reproduce at afaster than normal rate. Psoriasis produces red patches, sometimesreferred to as plaques, and dry grayish-white or silvery scales on apatient's skin.

A number of different treatments are currently employed to treatpsoriasis outbreaks. One of the more common treatments is the topicalapplication of corticosteroids to the affected area to reduce theinflammation. The patient may develop a resistance over time tocorticosteroids and therefore their use is often limited.

Other common treatments involve the topical application of anthralin,also known as dithranol, the topical application of a vitamin D such ascalcipotriene or calcitriol, or the topical application of a vitamin Asuch as tazarotene. It is believed that anthralin, vitamin D and vitaminA slow the patient's production of new skin cells. Anthralin can stain apatient's skin or clothing and does not work well on very activepsoriasis outbreaks. The topical applications of vitamins D and/or A maymake a patient sensitive to sun light.

Coal tar has also been used to treat psoriasis. The coal tar can beapplied directly to the affected area or it can be added to bath water.Although helpful, coal tar has a strong and unpleasant odor.

The topical application of salicylic acid has also been employed withsome psoriasis patients. Salicylic acid is believed to function as apeeling agent that will cause the outer layer of skin to shed. Salicylicacid may cause irritation and/or hair loss if left on the skin forextended periods of time.

Some psoriasis patients have also used ultraviolet light to treatpsoriasis. The ultraviolet light can involve the use of controlledamounts of natural sunlight on the exposed area or artificial sourcesdirected to the affected area.

Other patients have combined oral administration of psoralen, also knownas psoralene, with ultraviolet light treatments.

Still other psoriasis patients have used orally administered retinoids,i.e., very concentrated forms of vitamin A, or drugs that slow down thepatient's immune system such as methotrexate or cyclosporine.

Psoriasis patients are also advised to keep the skin moist by usingmoisturizing creams, lotions and soaps to help reduce the redness anditching associated with the psoriasis outbreaks or to use bath oils andsalts.

Although there are many potential treatment options for psoriasis, noneof the above mentioned methods are 100% successful or without adversepotentials.

It is an object of the present invention to provide a method fortreating psoriasis and to provide compositions that are useful intreating psoriasis without unpleasant odors or irritation to thepatient's skin.

SUMMARY OF THE INVENTION

The present invention accomplishes the above objectives and others byproviding a method of treating psoriasis comprising the topicalapplication of a composition comprising a sterol ester, preferablyC₁₀-C₃₀ carboxylic acid sterol esters, to the psoriatic area of apatient. The application of the composition will occur as needed butshould occur at least once daily and preferably immediately or shortlyafter, i.e., within 5, 10 or 15 minutes, washing and drying the affectedarea. The application of the composition to the psoriatic area shouldcontinue periodically until the psoriasis plaques and scales have beenremoved.

The composition may be applied to the psoriatic area in an unoccluded oroccluded manner. In one embodiment of the invention the compositionshould remain in contact with the psoriatic area for at least 20 minutesor longer, preferably at least 30 minutes or longer.

The composition may be a gel, cream, paste, lotion, ointment, salve,serum, spray, aerosol, mousse or foam. Preferably the composition is aserum, aerosol, mousse or foam.

In one embodiment of the present invention, the composition shouldcomprise 25% or more of a sterol ester, preferably a C₁₀-C₃₀ carboxylicacid sterol ester, based upon the total weight of the composition lesssolvent, preferably 30% or more based upon the total weight of thecomposition less solvent and most preferably 40% or more based upon thetotal weight of the composition less solvent.

In an alternative embodiment of the present invention, the compositionof the present invention will comprises a mixture of a sterol ester,preferably a C₁₀-C₃₀ carboxylic acid sterol ester, and a penetrationenhancer.

It is also believed that the compositions of the present invention arealso useful in treating skin disorders and afflictions such as eczema,sunburn, and wound and scar care

DETAILED DESCRIPTION OF THE INVENTION

As used herein, the term “psoriasis” refers to a dermatologicalcondition that is believed to be caused by the patient's body producingtoo many skin cells. The condition is associated with red patches, thickwhite/silvery scales and often swelling on the patient's skin, typicallyon the arms, scalp, ears and pubic area. It is believed that psoriasiscannot be cured but may be treated.

As used herein, the terms “treat” or “treating” refers to providingrelief of one or more of the conditions associated with psoriasis ordiminishing or lessening any one or more of the conditions associatedwith psoriasis.

As used herein, the terms “enhancement,” “penetration enhancement” and“permeation enhancement” mean an increase in the permeability of abiological membrane (e.g., skin or mucosa) to a drug or biologicallyactive substance, so as to increase the rate at which the drug orbiologically active substance permeates through the membrane.“Permeation enhancer,” “enhancer,” “penetration enhancer” or similarterms mean a material that achieves such permeation enhancement.

As used herein, “transdermal” means delivery of a drug or biologicallyactive substance by passage into and through the skin or mucosal tissue.Hence, the terms “transdermal” and “transmucosal” are usedinterchangeably unless specifically stated otherwise. Likewise, theterms “skin,” “derma,” “epidermis,” “mucosa” and the like will also beused interchangeably unless specifically stated otherwise.

As used herein, the term “topical” refers to outer skin or derma of apatient. Hence, the phrase “topical application” refers to theapplication of a composition of the present invention and its variousembodiments to the outer surface of a patient's skin or derma.

As used herein, the terms “occlude,” “occluded,” “occlusive” and thelike refer to a transdermal formulation that is applied to the skin withthe use of a supporting or otherwise associated structure. In otherwords, a topical formulation may be applied to the skin of a patientwith the aid of a structure, such as a backing member, bandage or cover.A matrix patch is an example of an occluded device. Conversely,“unoccluded” and “non-occluded,” which may be used interchangeably,refer to a transdermal formulation that is applied to the skin withoutthe use of a support, backing member, cover or otherwise associatedstructure. In other words, the transdermal formulation is applied to theskin in a free form, which is sufficient to effect transdermal deliveryof the drug or biologically active substance without the use ofstructures, such as a backing member, etc. A gel formulation is anexample of a non-occluded composition; other non-occluded compositionsinclude ointments, lotions, pastes, mousses, aerosols and creams.

The terms “combination” and “mixture” are used interchangeably andsynonymously. These terms should always be interpreted as over-inclusiverather than under-inclusive where appropriate.

Concentration, weight percent and other numerical data may be presentedherein in a range format. It is to be understood that such range formatis used merely for convenience and brevity and should be interpretedflexibly to include not only the numerical values explicitly recited asthe limits of the range, but also to include all the individualnumerical values or sub-ranges encompassed within that range as if eachnumerical value and sub-range is explicitly recited. For example, apercent range of 1% to 20% should be interpreted to include not only theexplicitly recited percent limits of 1% and 20% but also to includeindividual percentages such as 1.5%, 3%, 4.75%, 8.34% and sub-rangessuch as 1% to 5%, 10% to 15%, 4.7% to 11.9% etc.

The present invention is a method for treating psoriasis and acomposition that is useful for treating psoriasis.

The method comprises the topical application of a composition to thepsoriatic area of a patient suffering from a psoriasis outbreak. Thecomposition comprises a sterol ester, preferably a C₁₀-C₃₀ carboxylicacid sterol ester. The composition may be a gel, cream, paste, lotion,ointment, salve, serum, spray, aerosol, mousse or foam.

The method further comprises the steps of washing the psoriatic area,drying the psoriatic area and optionally exfoliating the psoriatic areaprior to the application of the composition. The method or topicalapplication of the composition should occur at least once a day or twicea day directly onto the psoriatic area. Three, 4, 5 or more applicationsof the composition to the psoriatic area may occur per day dependingupon the severity of the psoriasis outbreak and location on thepatient's body.

Depending upon the form in which the composition is applied, i.e., gel,serum or cream, after the application of the composition to thepsoriatic area, the composition and psoriatic area may be covered with aprotective cloth, bandage, gauze or wrap to prevent transfer of thecomposition to a patient's clothing, furniture or third parties. Theprotective cloth, bandage, gauze or wrap may also be applied to protectthe psoriatic area from dirt, germs and bacteria.

The method of the present invention is repeated every day or portion ofthe day as needed until the psoriasis outbreak has resided or ended.

The composition of the present invention comprises a sterol ester,preferably a C₁₀-C₃₀ carboxylic acid sterol ester, and most preferably aC₁₀-C₃₀ carboxylic acid cholesterol/lanosterol mixture commerciallyavailable from Croda Chemicals Europe, Ltd., of East Yorkshire, Englandunder the trade name SUPER STEROL ESTER®. It is believed that C₁₀-C₃₀cholesterol/lanosterol ester mixture sold by Croda Chemicals is derivedfrom wool wax by a process described in Koresawa et al., U.S. Pat. No.4,138,416, which is incorporated in its entirety herein by reference.Additional examples of sterol esters that may be used in the compositionof the present invention include but are not limited to stearate,palmitate, acetate, lanolate, macadamiate, nonanoate, oleate, butyrate,hydroxystearate, isostearate, sulfate, isostearate carbonate ofcholesterol and other sterols.

The amount of sterol ester in the composition of the present inventionshould comprise 25% or more of the sterol ester based upon the weight ofthe composition less solvent, preferably 30% or more based upon thetotal weight of the composition less solvent and most preferably 40% ormore based upon the total weight of the composition less solvent.Because numerous excipients in a transdermal formulation may have theability to impart multiple functions depending upon the concentrationand manner in which they are used, when determining the amount of sterolester less the amount of solvent present in a composition prepared inaccordance with the present invention, the solvents present in thecomposition but excluded from sterol ester weight percent calculations,are compounds that are liquids at room temperature and have a boilingpoint below 150° C. under normal atmospheric conditions, preferably aboiling point below 125° C. and most preferably a boiling point below105° C. Examples of typical solvents that should be excluded from thesterol weight percent calculations are water, low molecular weightalcohols such as C₁-C₆ branched or straight chain alcohols, e.g.,methanol, ethanol and isopropanol, low molecular weight ketones such asC₁-C₆ branched or straight chain ketones, e.g., acetone, aromaticcompounds and low molecular weight alkanes such as C₁-C₁₀ branched orstraight chain alkanes.

The compositions of the present invention may further comprise apenetration enhancer. The amount of penetration enhancer employed in thecompositions of the present invention will vary depending upon thespecific composition embodiment or transdermal formulation, i.e., serum,cream or foam, and the specific penetration enhancer selected.Typically, the amount of penetration enhancer employed in thecompositions of the present invention should be about 0.001 wt % toabout 25 wt %, preferably about 0.005 wt % to about 15 wt % and mostpreferably about 0.01 wt % to about 10 wt % based upon the total weightof the composition. Examples of penetration enhancers that may be usedin compositions of the present invention include, but are not limitedto, fatty acids, fatty acid esters, fatty alcohols, fatty acid esters oflactic acid or glycolic acid, glycerol tri-, di- and monoesters,triacetin, short chain alcohols, amine oxides and mixtures thereof.Particular examples of permeation enhancers include oleyl alcohol,lauryl alcohol, isopropyl myristate, oleyl oleate, levulinic acid,ethanol, glycerol monooleate, methyl laurate, sorbitain monooleate,triacetin, aloe vera oil, benzothonium chloride, cetyl dimethylamineoxide, cetyl alcohol, cetyl lactate, cocamidopropyl betaine, cocoamineoxide diethanolamine, dimethyloctylamine oxide,2-dodecoxyethyldimethylamine oxide, dimethyl-decylamine oxide,dimethylhexadecylamine oxide, dimethyl-tetradecylamine oxide, dimethylisosorbide, dipropylene glycol, ethyl hexyl lactate, glycolic acid,3-dodecoxy-2-hydroxypropyldi(3-hydroxypropyl)amine oxide, lactic acid,lauramine oxide, lauryl betaine, lauryl lactate, lauryl laurate,isopropyl palmitate, macrogol 15 hydroxystearate (Solutol HS 15),menthol, menthyl lactate, myristyl alcohol, myristal lactate,octyldodecanol, octyl salicylate, oleamine oxide, oleic acid, oleylbetaine, oleyldi(2-hydroxyethyl) amine oxide, PEG 1000,pentadecalactone, propylene glycol, salicylic acid, stearyl alcohol,stearyl lactate, 3,6,9-trioxaheptadecyldiethylamine oxide,di(2-hydroxyethyl)-tetradecylamine oxide, triethanolamine triacetate andcombinations thereof. Other permeation enhancers useful with the presentinvention may be found in U.S. Patent Application Publication No.2007/0269379, which is incorporated in its entirety herein by reference.Preferred permeation enhancers include oleyl alcohol, lauryl alcohol,isopropyl myristate, oleyl oleate, levulinic acid, glycerol monooleate,methyl laurate, sorbitain monooleate, triacetin, cetyl alcohol, cetyllactate, dimethyl isosorbide, dipropylene glycol, ethyl hexyl lactate,glycolic acid, lauramine oxide, lauryl betaine, lauryl lactate, lauryllaurate, isopropyl palmitate, myristyl alcohol, myristal lactate, octylsalicylate, oleamine oxide, oleic acid, oleyl betaine, salicylic acid,stearyl alcohol, stearyl lactate, triethanolamine triacetate andcombinations thereof.

Depending upon the specific composition embodiment or transdermalformulation, i.e., serum, cream or foam, the composition of the presentinvention may also include further additives such as solvents, filmforming/polymeric agents, viscosity increasing agents, emulsifiers,antioxidants, preservatives, pH adjusting agents, propellants andcombinations of the forgoing.

The compositions of the present invention may include any suitablesolvent. Preferably, the solvent may include water and/or one or moreorganic compounds, e.g., esters, terpenes, alcohols, ketones, aldehydes,fatty acids, partially or fully esterified fatty acids, wherein thestructures are cyclic, non-cyclic (e.g., alkyl), alicyclic (i.e., abridged ring compound), or aromatic, as well as organic compounds havingcombinations of these functional groups. Specific examples of solventsthat may be employed are water, methanol, ethanol, isopropyl alcohol,acetone, hexane, butyl alcohol, ethyl acetate, polyethylene glycol,propylene glycol, ethylene glycol, triethylene glycol, glycerin,1,3-propane diol, 2-methyl-1,3-propane diol, glycerol ricinoleate,mineral oil, peanut oil, corn oil, cottonseed oil, sesame oil or acombination thereof. The solvent may be employed in any suitable amount.Typically, the solvent can be present in the composition in about 1.0 wt% to about 95.0 wt % based upon the total weight of the composition,preferably about 3.0 wt % to about 85 wt % based upon the total weightof the composition and most preferably about 5.0 wt % to about 75 wt %of the total weight of the composition.

The compositions of the present invention also may include afilm-forming/polymeric agent. Although applicants do not wish to bebound by an particular theory, it is believed that the presence of afilm-forming/polymeric agent in the compositions prepared in accordancewith the present invention allow the compositions to spread more easilyover the skin and to form a protective barrier coating allowing thesterol ester to penetrate the skin of the psoriatic area and/or remainin contact with the skin of the psoriatic area. Thefilm-forming/polymeric agent may also enhance the adherence of thecomposition to the patient's skin and improve the composition'sresistance to wash off or rub off.

Film-forming/polymeric agents are preferably soluble or miscible withthe sterol ester and/or penetration enhancer. The composition of thepresent invention typically comprises from about 0.001 wt % to about 25wt %, preferably about 0.005 wt % to about 15 wt % and most preferablyabout 0.010 wt % to about 10 wt % based upon the total weight of thecomposition. Some examples of film-forming/polymeric agents that may beused in compositions of the present invention are polyalkenes,oleophilic copolymers of vinvylpyrrolidone, acrylic copolymers,polyethylene glycol derivative, polyolefins, polyurethanes and mixturesthereof.

Examples of polyalkenes that may be included in the compositions of thepresent invention are polyethylenes having a molecular weight rangingfrom about 300 to about 3000 (available as PERFORMALENE® from New PhaseTechnologies, Piscataway, N.J.); polyisobutylenes (available asVISTANEX™ from Exxon Chemical Company, Houston, Tex.); polyisobutenes(available as PRESPERSE™ from Sumitomo Corp.); polydecenes (SILKFLO™available from Amoco); and hydrogenated polyisobutenes (PANALANE®available from Lipo Chemicals, Inc., Paterson, N.J.).

Oleophilic copolymers of vinylpyrollidone suitable for use in thecompositions of the present invention may be copolymers ofpolyvinylpyrrolidone (PVP) and long chain alpha olefins, including, butnot limited to, PVP/eicosene copolymers (GANEX® V-220 and V-220F), andtricontanyl PVP copolymers (GANEX®) available from Ashland, formerlyInternational Specialty Products, Wayne, N.J.

Examples of acrylic copolymers that may be used in the compositions ofthe present invention include acrylic copolymers having long (C₈-C₃₀)alkyl chains to enhance their oleophilicity, such asacrylate/octylacrylamide copolymers (available as DERMACRYL® from AkzoNobel). An example of a polyethylene glycol derivative that may be usedas a film forming agent in compositions of the present invention is apolyethylene glycol derivative of Beeswax (ESTOL® E04BW-3752, E06BW-3753or E03BW-3751 formerly available from Unichema, Wilmington, Del. andcurrently available from Croda under the trade name CITHROL®). Examplesof polyolefins that may be used as a film forming agent in compositionsof the present invention are fatty acid ester/fatty acid anhydridegrafted polyolefins wherein the esters and anhydrides are derived fromC₁₂-C₂₂ fatty acid moieties, for example, C₃₀-C₃₈ olefin/isopropylmaleate/maleic anhydride copolymer (PERFORMA™ V1608, available from NewPhase Technologies, Piscataway, N.J.).

A preferred group of film forming/polymeric agents that may be used inthe compositions of the present invention include polyurethanes derivedfrom isophorone di-isocyanate such as those described in U.S. Pat. Nos.5,051,260 and 6,613,866 and sold by Alzo International Inc. under thetradename POLYDERM®, polyisobutene/polybutene, hydrogentated polydeceneand hydrogenated C₆-C₁₄ olefin polymers sold by ExxonMobil Chemicalcompany under the tradename PURESYN®. The following table identifies afew of the preferred film forming/polymeric agents:

Commercial Name Chemical Description Origin POLYDERM ® PPI-BZ BenzylAlcohol-Ethylene Alzo International Inc. Glycol/IPDI CopolymerPOLYDERM ® PPI-CA-15 Di-PEG-15 Cocamine/IPDI Alzo International Inc.Copolymer POLYDERM ® PPI-CO Castor Oil/IPDI Copolymer Alzo InternationalInc. POLYDERM ® PPI-CO-H Hydrogenated Castor Oil/IPDI Alzo InternationalInc. Copolymer POLYDERM ® PPI-CO-40 PEG-40 Hydrogenated Castor AlzoInternational Inc. Oil/IPDI Copolymer POLYDERM ® PPI-CO-200 PEG-200Hydrogenated Castor Alzo International Inc. Oil/IPDI CopolymerPOLYDERM ® PPI-DGDIS Diglycerol Diisostearate/IPDI Alzo InternationalInc. Copolymer POLYDERM ® PPI-GH Glycereth-7 Hydroxystearate/IPDI AlzoInternational Inc. Copolymer POLYDERM ® PPI-PE Diethylene GlycolAdipate/IPDI Alzo International Inc. Copolymer POLYDERM ® PPI-SA Di-2PEG Soyamine/IPDI Alzo International Inc. Copolymer POLYDERM ® PPI-SIDimethiconol/IPDI Copolymer Alzo International Inc. POLYDERM ® PPI-SI-50Dimethiconol/IPDI Copolymer Alzo International Inc. 50% POLYDERM ®PPI-SI/SA Dimethiconol-PEG-2 Alzo International Inc. Soyamine/IPDICopolymer POLYDERM ® PPI-SI-WI Dimethicone Copolyol/IPDI AlzoInternational Inc. Copolymer water insoluble POLYDERM ® PPI-SI-WSDimethicone Copolyol/IPDI Alzo International Inc. Copolymer watersoluble AVALURE ® UR 450 PPG-17/IPDI/DMPA Noveon Copolymer POLYSYNLANE ®Gel Hydrogenated Polyisobutene Collaborative Group (and)Butylene/Ethylene/Styrene Copolymer (and) Ethylene/ Propylene/StyreneCopolymer POLYFIX ® JPN Hydrogenated Polyisobutene Collaborative Group(and) Polybutene POLYSYNLANE ® (HV) Hydrogenated PolyisobuteneCollaborative Group PANALENE ® H300E Lipo Chemicals PANALENE ® L-14ELipo Chemicals PURESYN ® 2, 4, 6, 8, Polydecene or HydrogenatedExxonMobil Chemicals 10, 40, 100, 150, 300 Polydecene 1000, 3000

The preferred film forming/polymeric agents are water-insoluble,oleophilic and/or water-resistant.

The compositions of the present invention may also contain viscosityenhancing agents that thicken, gel or harden the composition. Thecomposition of the present invention typically comprises from about0.001 wt % to about 50 wt % of the viscosity enhancing agent, preferablyabout 0.005 wt % to about 40 wt % and most preferably about 0.01 wt % toabout 25 wt % based upon the total weight of the composition. Exemplaryviscosity enhancing agents include organic materials such as natural orsynthetic waxes, C₁₂-C₆₀ alcohols, C₁₂-C₆₀ acids, alpha-hydroxy fattyacids, polyhydroxy fatty acid esters, polyhydroxy fatty acid amides, andinorganic/organic materials such as metal ester complexes containingzinc, calcium, aluminum or magnesium, fumed silicas, and organoclays.Additional viscosity enhancing agents include polyol polyesters,glyceryl esters, polyglyceryl esters and polysiloxanes that are a solidor semi-solid at ambient temperature.

Specific examples of viscosity enhancing agents that may be included inthe compositions of the present invention include C₁₂-C₆₀ alcohols,preferably C₁₆-C₂₂ fatty alcohols, such as cetyl alcohol, stearylalcohol, behenyl alcohol and mixtures thereof. Other suitable viscosityenhancing agents include C₁₂-C₆₀ acids, preferably C₁₆-C₂₂ fatty acids,such as palmitic acid, stearic acid, behenic acid, oleic acid, linoleicacid, myristic acid, ricinoleic acid, eurcic acid, lauric acid,isostearic acid and mixtures thereof. Further suitable viscosityenhancing agents that may be used herein are alpha-hydroxy fatty acids,including 12-hydroxystearic acid, 12-hydroxylauric acid,16-hydroxyhexadecanoic acid and mixtures thereof. Additional examples ofsuitable fatty acids are further described in Klofta et al., U.S. Pat.No. 7,449,613, Hofrichter, et al., U.S. Pat. No. 5,429,816 and Motley,U.S. Pat. No. 5,552,136, disclosure of each is incorporated in itsentirety herein by reference.

Waxes are also suitable for use as viscosity enhancing agents incompositions of the present invention. Natural waxes may include, butare not limited to, carnauba, ozokerite, beeswax, candelilla, paraffin,ceresin, esparto, ouricuri, rezowax and other known mined and mineralwaxes. Synthetic waxes may include, but are not limited to, paraffinwaxes and microcrystalline waxes.

Additional viscosity enhancing agents that may be used herein includepolyhydroxy fatty acid esters, polyhydroxy fatty acid amides andmixtures thereof. Preferred esters and amides will have three or morefree hydroxy groups on the polyhydroxy moiety and are typically nonionicin character. Because of the possible skin sensitivity of those usingarticles to which the composition is applied, these esters and amidesshould also be relatively mild and non-irritating to the skin. Suitablepolyhydroxy fatty acid esters and polyhydroxy fatty acid amides aredisclosed in Roe et al., U.S. Pat. No. 5,643,588, the disclosure ofwhich is incorporated in its entirety herein by reference.

Still further viscosity enhancing agents that may be included in thecompositions of the present invention are gelling agents. Gelling agentsare materials that can swell or expand when in contact with water.Examples of gelling agents that may be used in the present inventioninclude swellable polymers, also known as osmopolymers or hydrogels. Theswellable polymer can be non-cross-linked or lightly cross-linked. Thecross-links can be covalent or ionic bonds with the polymer possessingthe ability to swell in the presence of fluid, and when cross-linked itwill not be dissolved in the fluid. The polymer can be of plant, animalor synthetic origin. Polymeric materials useful for the present purposeinclude polyhydroalkylcellulose having a molecular weight greater than50,000, such as hydroxyl propylmethylcellulose (METHOCEL® K 100Mavailable from Dow Chemical); poly(hydroxyalkylmethacrylate) having amolecular weight of from 5,000 to 5,000,000; poly(vinylpyrrolidone)having a molecular weight of from 100,000 to 3,000,000; anionic andcationic hydrogels; poly(electrolyte) complexes; poly(vinylalcohol)having a low acetate residual; a swellable mixture of agar andcarboxymethyl cellulose; a swellable composition comprising methylcellulose mixed with a sparingly cross-linked agar; a polyether having amolecular weight of from 10,000 to 6,000,000; a water-swellablecopolymer produced by a dispersion of a finely divided copolymer ofmaleic anhydride with styrene, ethylene, propylene, or isobutylene; awater-swellable polymer of N-vinyl lactams and the like.

Other gelling agents useful in the present invention include pectinhaving a molecular weight ranging from 30,000 to 300,000;polysaccharides such as agar, acacia, karaya, tragacanth, algins andguar; CARBOPOL®, an acrylic acid polymer, a carboxyvinyl polymer,sometimes referred to as carboxypolymethylene, a polymer of acrylic acidcross-linked with a polyallyl ether of sucrose, as described in U.S.Pat. Nos. 2,798,053 and 2,909,462 and available as CARBOPOL® 934, 940and 941, and its salt derivatives; polyacrylamides; water-swellableindene maleic anhydride polymers; GOOD-RITE® polyacrylic acid having amolecular weight of 80,000 to 200,000; POLYOX® polyethylene oxidepolymers having a molecular weight of 100,000 to 7,000,000; starch graftcopolymers; AQUA-KEEP® acrylate polymers with water absorbability ofabout 400 times its original weight; diesters of polyglucan; a mixtureof cross-linked polyvinyl alcohol and poly(N-vinyl-2-pyrrolidone);poly(ethylene glycol) having a molecular weight of 4,000 to 100,000.Representative polymers possessing gelling properties are described inU.S. Pat. Nos. 6,419,954, 4,915,949, 4,327,725, 4,207,893 and inHandbook of Common Polymers, by Scott and Roff, published by ClevelandRubber Company, Cleveland, Ohio.

Examples of inorganic viscosity enhancing agents that may be included inthe compositions of the present invention include treated and untreatedfumed silicas such as those available from Cabot Corp., Tuscola, Ill.under the trade designations CAB-O-SIL M5 and MS-55. Exemplarysurface-treated fumed silicas are also available from Cabot Corp.,Tuscola, Ill. under the trade designations TS-720 and TS-610.

Suitable clays such as hectorite and smectite may also be used asviscosity enhancing agents in compositions of the present invention.

Hydrogenated vegetable oils such as cocoa butter, shea butter andmixtures thereof may also be used as viscosity enhancing agents incompositions of the present invention.

Suitable petroleum-based emollients may also be used as viscosityenhancing agents in compositions of the present invention. Examples ofsuitable petroleum-based emollients that may be used includepetrolatums, i.e., hydrocarbons or mixtures of hydrocarbons;particularly preferred are hydrocarbons having chain lengths of from C₁₀to C₁₀₀. Petroleum-based emollients within this chain length rangeinclude mineral oil and petrolatum. Mineral oil usually refers to lessviscous mixtures of hydrocarbons having from 10 to 30 carbon atoms,though the hydrocarbon molecular weight distribution may vary. Since thelower molecular weight hydrocarbons can cause irritation in someindividuals, mineral oils having a small percentage of lower molecularweight hydrocarbons are preferred. Petrolatum usually refers to moreviscous mixtures of hydrocarbons of higher molecular weighthydrocarbons. Petrolatum and mineral oil are preferred skin conditioningagents for compositions of the present invention due to their ability toprotect the skin from harmful or irritating stimuli. Petrolatum isparticularly preferred because of its good barrier properties.

The compositions of the present invention may also contain humectants.The compositions of the present invention typically comprises from about0.001 wt % to about 30 wt % of a humectant, preferably about 0.005 wt %to about 20 wt % and most preferably about 0.01 wt % to about 10 wt %based upon the total weight of the composition. Examples of compoundsthat may be used as humectants in compositions of the present inventionare esters of polyhydroxy alcohols. This type of ester may includeglyceryl esters including glycerides and derivatized glycerides,polyglyceryl esters, and glycolic esters. Glyceryl esters are derivedfrom glycerin, its derivatives and one or more carboxylic acid moieties.Non-limiting examples include various C₁-C₃₀ mono-, di- or tri-esters ofglycerin and derivatives thereof, such as mono-, di-, tri-glycerides,acetoglycerides, and ethoxylated glycerides. Exemplary glyceryl estersinclude glyceryl behenate, glyceryl oleate, glyceryl stearate, glycerylpalmitate, glyceryl distearate, glyceryl dipalmitate and the like.Polyglyceryl esters having C₁₂-C₂₂ acid moieties are also suitable foruse herein. Non-limiting examples include polyglyceryl-4 isostearate,polyglyceryl-3 oleate, diglyceryl monooleate, tetraglyceryl monooleateand the like. Glycolic esters are derived from C₂-C₆ glycols, includingethylene glycol, propylene glycol, butylene glycol, hexylene glycol andderivatives thereof, and one or more carboxylic acid moieties havingC₁-C₃₀ chains. Specific examples of glycolic esters include polyethyleneglycols (PEGs), such as PEG-2, PEG-3, PEG-30 and PEG-50, andpolypropylene glycols (PPGs), such as PPG-9, PPG-12, PPG-15, PPG-17,PPG-20, PPG-26, PPG-30 and PPG-34.

The compositions of the present invention may also contain emulsifiersor dispersing agents such as anionic, cationic and nonionic surfactants.The compositions of the present invention typically comprises from about0.001 wt % to about 15 wt % of an emulsifier or dispersing agent,preferably about 0.005 wt % to about 10 wt % and most preferably about0.01 wt % to about 5 wt % based upon the total weight of thecomposition. Nonionic surfactants are preferred because of their lowlevel of irritation to skin. Typical nonionic surfactants aremonoglycerides such as glyceryl monostearate and the like; sorbitanaliphatic esters such as sorbitan monolaurate and the like; sucrosealiphatic esters; polyoxyethylene aliphatic esters such aspolyoxyethylene stearate; and polyoxyethylene higher alcohol ethers suchas polyoxyethylene cetyl ether, polyoxyethylene oleyl ether,polyoxyethylene fatty ethers and the like.

The compositions of the present invention may also contain anantioxidant to minimize or prevent the oxidation process and enhance theshelf life of the composition. The compositions of the present inventiontypically comprises from about 0.001 wt % to about 25 wt % of ananti-oxidant, preferably about 0.005 wt % to about 15 wt % and mostpreferably about 0.01 wt % to about 10 wt % based upon the total weightof the composition. Antioxidants useful herein should preferably be mildand non-irritating. Antioxidants from natural sources are preferred,such as Vitamin E and its derivatives, including tocopherol, tocopherolacetate, mixed tocopherols (available as COVI-OX T-50 or T-70 fromHenkel Corp, Ambler, Pa.), and the like or butylated hydroxytoluene,butylated hydroxyanisole, sodium pyrosulfite, acetone sodium bisulfateand the like. Some of these antioxidants are also useful as skinantioxidants, which minimizes the wrinkles and dullness of the skin andprovides a more youthful looking and firmer textured skin.

The compositions of the present invention may also contain apreservative to prevent bacterial growth and odors thereof, particularlyin compositions having a relatively high water content. The compositionsof the present invention typically comprise from about 0.001 wt % toabout 10 wt % of a preservative, preferably about 0.005 wt % to about 5wt % and most preferably about 0.01 wt % to about 2.5 wt % based uponthe total weight of the composition. Suitable preservatives includepropyl paraben, methyl paraben, benzyl alcohol, benzalkonium chloride,tribasic calcium phosphate, phenoxyethanol, or acids such as citric,tartaric, maleic, lactic, malic, benzoic, salicylic and the like.

The compositions of the present invention may include an acid or base toadjust the pH of the composition to the desired or optimal range.Examples of compounds typically used to adjust the pH of topicalcompositions include oleic acid, hydrochloric acid, citric acid, lacticacid, tartaric acid, glacial acetic acid, sodium hydroxide or the like.Depending upon the form in which the composition is applied, i.e., gel,serum or cream, and the location, the desired final pH value of thecomposition may vary, however, it is generally preferred that thecomposition range from a pH of about 5.0 to about 8.5, preferably about6 to about 8.0 and most preferably about 6.5 to about 7.5.

In order to increase the stability of the compositions of the presentinvention, it may be necessary to add a chelating agent. The chelatingagents may include ethylenediaminetetraacetic acid (EDTA) and itsderivatives, thioglycolic acid, thiolactic acid, thioglycerol and thelike.

A fragrance may also be added to composition of the present invention ifdesired.

If the composition of the present invention is an aerosol, foam ormouse, the composition will require a propellant for dispensing thecomposition from the container. The propellant may be any type ofpropellant commonly used in the cosmetic/pharmaceutical industry such asnitrogen, carbon dioxide, dimethyl ether, hydrocarbons, i.e., methane,ethane, propane, butanes and pentanes, halogenated hydrocarbons, i.e.,CH₂ClF, CClF₂CHClF, CF₃CHClF, CHF₂CClF₂, CHClFCHF₂, CF₃CH₂C₁, CClF₂CH₃,CHF₂CHF₂, CF₃CH₂F (HFC 134a), CHF₂CH₃ (HFC 152a), CF₃CHFCF₃ (HFC 227),CF₃CF₃ and CF₃CF₂CF₃. Some of the more commonly used hydrocarbonpropellants are A-46 (15.2% propane/84.8% isobutene); and NP-46 (25.9%propane/74.1% n-butane), NIP-46 (21.9% propane/31.3% isobutene/46.8%n-butane). The amount of propellant will depend on the type of containerfor the composition of the present invention, the amount of thecomposition in the container, the amount of composition to be dispensedper actuation and the form in which the composition will be dispensed,i.e., mist or foam. The optimization of the propellant and container arewithin the ability of the skilled artisan and examples can be found inWai-Chiu So et al., U.S. Pat. No. 6,946,120 and Remington, Science andPractice of Pharmacy, 21^(st) ed., pp. 1000-1017 which are incorporatedin their entirety herein by reference. The propellant is generally notincluded in the calculation of the weight percentages of the compositionprepared in accordance with the present invention because it is merelypart of the dispensing device and typically does not remain part of thecomposition once the composition is dispensed and applied to thepatient's psoriatic area.

The aerosols, foams and mousses of the present invention will include asolvent, preferably water and/or a lower alcohol, i.e., C₁-C₆ alcoholssuch as methanol, ethanol, isopropanol or mixtures thereof. Theaerosols, foams or mousses may also comprise a co-solvent selected fromone or more of the group consisting of aromatic and polyhydric alcoholssuch as 1,3-butylene glycol, propylene glycol, polyethylene glycol 400,hexylene glycol and dipropylene glycol or glycerol. When the co-solventis present, it may be present in amounts of approximately 10% by weightor less, preferably approximately 5% by weight or less based upon thetotal weight of the composition.

The composition of the present invention may also include ananti-inflammatory drug, a topical anesthetic or a combination thereof.Typical topical anesthetics include, but are not limited to, lidocaine,xylocaine, buprenorphine and fentanyl. Suitable topical anesthetics areknown to those of skill in the art and are disclosed, e.g., in GoodmanGilman, Alfred; Goodman, Louis S.; Gilman, Alfred; Goodman and Gilman'sThe Pharmacological Basis of Therapeutics, Ninth Edition, pp. 331-347.

Any suitable topical corticosteroid can be employed as ananti-inflammatory drug. Suitable corticosteroids are known to those ofskill in the art and are disclosed in, e.g., Goodman Gilman, Alfred;Goodman, Louis S.; Gilman, Alfred; Goodman and Gilman's ThePharmacological Basis of Therapeutics, Ninth Edition, pp. 1459-1483.Suitable exemplary corticosteroids include cortisol (hydrocortisone);tetrahydrocortisol; prednisone (cortisone); prednisolone (cortisol);6α-methylprednisolone; fludrocortisone (9α-fluorocortisol);11-desoxycortisol; cortisone (11-dehydrocortisol); corticosterone;triamcinolone (9α-fluoro-16α-hydroxyprednisolone); paramethasone(6α-fluoro-16α-methylprednisolone); betamethasone(9α-fluoro-16β-methylprednisolone); dexamethasone(9α-fluoro-16α-methylprednisolone); desoxycorticosterone acetate (docaacetate, percorten acetate); desoxycorticosterone pivalate (percortenpivalate); fludrocortisone acetate (florine acetate); cortisol(hydrocortisone) (cortef, hydrocortone); cortisol acetate (cortefacetate, hydrocortone acetate); cortisol cypionate (cortef); cortisolsodium phosphate (hydrocortone phosphate); cortisol sodium succinate(solu-cortef); beclopmethasone dipropionate (vanceril); betamethasone(celestone); betamethasone sodium phosphate and acetate (celestonesoluspan); betamethasone dipropionate (diprosone); betamethasonevalerate (valisone); betamethasone benzoate (benisone, flurodate);cortisone acetate (cortone acetate); dexamethasone (decadron,gammacorten); dexamethasone sodium phosphate (decadron phosphate,hexadrol phosphate); dexamethasone acetate (decadron-L.A.);fuprednisolone (alphadrol); meprednisone (betapar); methylprednisolone(medrol); methylprednisolone acetate (depo-medrol, medrol acetate);methylprednisolone sodium succinate (solu-medrol); paramethasone acetate(haldrone); prednisolone (delta-cortef); prednisolone acetate(meticortelone acetate); prednisolone sodium phosphate (hydeltrasol);prednisolone sodium succinate (meticortelone soluble); prednisolonetebutate (hydelta-T.B.A.); prednisone (deltasone, paracort);triamcinolone (aristocort, kenacort); triamcinolone acetonide(aristoderm, kenalog); triamcinolone diacetate (aristocort diacetate,kienacort diacetate); triamcinolone hexacotonide (aristospan); desonide(tridesilon); desoximetasone (topicort); flumethasone pivalate(locorten); fluocinolone acetonide (fluonid, synalar); fluocinonide(lidex, topsyn); fluorometholone (oxylone); flurandrenolide (cordran);halcinonide (halog); and medrysone (HMS liquifilm, medrocort).

Preferably, the amount of a suitable topical anti-inflammatory ortopical anesthetic can be present in about 0.1 wt % to about 99.9 wt %of the composition. Typically, the amount of anesthetic and/oranti-inflammatory present will depend upon the specific anesthetic andanti-inflammatory employed in the composition. In some embodiments ofthe present invention, the anesthetic and/or anti-inflammatory can be upto about 10 wt %, up to about 5 wt %, up to about 2 wt %, up to about 1wt % or up to about 0.1 wt % of the composition. Additionally, thenature and amount of the anesthetic and/or anti-inflammatory present inthe composition should comply with any State and/or Federal guidelinesthat regulate the use of such compounds (e.g., FDA regulations).

The compositions of the present invention may also include knownpsoriasis treatment agents such as anthralin, also known as dithranol,vitamin D such as calcipotriene or calcitriol, and vitamin A such astazarotene. Some of the known psoriasis treatment agents are describedin greater detail in Goodman Gilman, Alfred; Goodman, Louis S.; Gilman,Alfred; Goodman and Gilman's The Pharmacological Basis of Therapeutics,Ninth Edition, pp. 1591-1613.

The following tables provide a summary overview of a few representativecompositions that can be prepared in accordance with the presentinvention and is not intended to limit the present invention:

Serum Preferred Most Preferred Ingredient Weight % Weight % Sterol Ester75-99%  80-95%  Penetration Enhancer 0.01-15%   0.1-10%  Film-Forming/0.1-10%  0.5-5% Polymeric Agent Antioxidant 0-10% 0.5-5% Preservative0-10% 0.5-5% Vitamin(s) 0-25%  0-15%

Salve Preferred Most Preferred Ingredient Weight % Weight % Sterol Ester40-90%  60-85%  Penetration Enhancer 0.01-15%   0.1-10%  Film-Forming/0.1-10%  0.5-5% Polymeric Agent Viscosity Enhancing 5-40% 10-25%  AgentAntioxidant 0-10% 0.5-5% Preservative 0-10% 0.5-5% Vitamin(s) 0-25% 0-15%

Cream/Lotion/Gel Preferred Most Preferred Ingredient Weight % Weight %Sterol Ester (30-80%)*  (40-70%)* Penetration Enhancer 0.01-15%  0.1-10%  Film-Forming/ 0.1-10%  0.5-5% Polymeric Agent ViscosityEnhancing 1-40%  3-20% Agent Solvent 5-85% 10-75%  Emulsifier 0.1-20%  1-10% Antioxidant 0-10% 0.5-5% Preservative 0-10% 0.5-5% *weightpercent based upon amount of sterol ester less solvent

Aerosol/Mousse/Foam Preferred Most Preferred Ingredient Weight % Weight% Sterol Ester (30-75%)*   (35-60%)* Penetration Enhancer 0.001-10%   0.002-5% Film-Forming/ 0.001-10%    0.005-5% Polymeric Agent ViscosityEnhancing 0.001-30%    0.005-20%  Agent Solvent 50-95%   60-90%Emulsifier 0.1-20%    1-10% Propellant 0.5-25%    1-10% Antioxidant0-10% 0.001-5% Preservative 0-10% 0.001-5% *weight percent based uponamount of sterol ester less solvent

EXAMPLES

The following are provided by way of example only and are by no meansintended to be limiting.

Example 1

A serum with the following composition is prepared:

SUPER STEROL LIQUID 91.5 wt % Shea Butter 1.0 wt % Lauryl Laurate 2.5 wt% POLYDERM PPI-SA 1.0 wt % Oleic Acid 1.0 wt % Vitamin-A Palmitate 1.0wt % Vitamin -E Acetate 1.0 wt % Phenoxyethanol 1.0 wt %

The serum is prepared by adding the SUPER STEROL LIQUID, shea butter,POLYDERM PPI-SA, oleic acid and lauryl laurate to a suitable mixer andheating the mixture at 75-85° C. for about 30 minutes until a clearsolution is obtained. The SUPER STEROL LIQUID is commercially availablefrom Croda Chemicals Europe, Ltd., of East Yorkshire, England and is amixture of C₁₀-C₃₀ cholesterol and lanosterol esters. POLYDERM PPI-SA isa Di-PEG-2 Soyamine/IPDI copolymer commercially available from AlzoInternational Inc.

The resulting composition is removed from the heat and the stirring iscontinued. Once the temperature of the composition is 50° C. or lower,vitamin A palmitate, vitamin E acetate and phenoxyethanol are added tothe composition while stirring is maintained. Once the compositionobtains room temperature, the serum composition is packaged in a pumpbottle.

Example 2

A salve with the following composition is prepared:

SUPER STEROL SOLID 75 wt % Shea Butter 15 wt % Lauryl Laurate 2.5 wt %POLYDERM PPI-SA 2.5 wt % Oleic Acid 1.0 wt % Vitamin-A Palmitate 1.5 wt% Vitamin -E Acetate 1.5 wt % Phenoxyethanol 1.0 wt %

The above salve is prepared by mixing the above ingredients in asuitable mixer by the procedure outlined in Example 1 and filling theslave into a suitable tube for dispensing by the patient.

Example 3

A cream is with the following composition is prepared:

SUPER STEROL LIQUID 18.3* wt % Shea Butter 0.2 wt % Lauryl Laurate 0.5wt % POLYDERM PPI-SA 0.2 wt % Oleic Acid 0.2 wt % Vitamin-A Palmitate0.2 wt % Vitamin -E Acetate 0.2 wt % Phenoxyethanol 0.2 wt % POLAWAX ™10.0 wt % Water 68.5 wt % Cetyl Alcohol 1.4 wt % DOWICIL ™-200 0.1 wt %*58.1% less the solvent (water)

The cream is prepared by adding the serum of Example 1, the POLAWAX™water and cetyl alcohol to a suitable mixer and heating the mixture at75-85° C. for about 20-30 minutes. POLAWAX™ is a higher fatty alcoholself-emulsifying wax commercially available from Croda Chemicals Europe,Ltd., of East Yorkshire, England. DOWICIL™-200 is a1-3-chloroallyl-3,5,7-triaza-1-azoniaadamantane chloridepreservative/anti-microbial compound commercially available from DowChemical Co. The resulting composition is removed from the heat and thestirring is continued. Once the solution obtains room temperature, theDOWICIL™-200 is added and the cream is packaged in a tube, jar, bottleor other suitable container.

Example 4

A foam with the following composition is prepared:

SUPER STEROL LIQUID 9.15* wt % Shea Butter 0.01 wt % Lauryl Laurate0.025 wt % POLYDERM PPI-SA 0.01 wt % Oleic Acid 0.01 wt % Vitamin-APalmitate 0.01 wt % Vitamin -E Acetate 0.01 wt % Phenoxyethanol 0.01 wt% Glycerox 767 10.0 wt % Water 80.0 wt % *45.75% less solvent (water

The above foam composition is prepared by adding the serum of Example 1,GLYCEROX 767 and water to a suitable mixer and heating the mixture at75° C. for about 10 minutes. GLYCEROX 767 is a PEG-6 capric/caprylicglycerides commercially available from Croda Chemicals Europe, Ltd., ofEast Yorkshire, England. The resulting composition is removed from theheat and stirred until it obtains room temperature. The composition isfilled into a sealed aerosol container along with A-46 propellant (15.2%propane/84.8% isobutene) commercially available from Diversified CPCInternational. The final aerosol container comprises approximately 96.5%of the above foam composition and 3.5% of the propellant with a pressureof about 46 PSIG @ 75° F.

Example 5

The serum prepared in Example 1 was applied 14 patients suffering frompsoriasis. The treatment regimen and results are summarized in the TABLE1.

TABLE 1 Affected Tx Previous Subject Age Sex Area Duration Tx TreatmentResult 01 13 F right 1 day One AQUAPHOR ® Complete y.o. knee treatment(OTC) used for resolution. behind dry skin right hydrocortisone knee 1%behind left knee 02 41 M upper 10 Pt. applied Pt. declined Pt. y.o. backmonths serum, monoclonal recovered lower exfoliator, antibody tx at 100%but back and wash Mayo Clinic and still has chest 3x/wk at other optionsat residual small home the Rockefeller pre- area on University to tryexisting face the serum. scars. stomach. 03 41 M left 14 Pt. applied Pt.declined i.v. Left and y.o. forearm months serum clinical trial tx atright left everyday at Mayo Clinic to forearm, elbow home in try theserum. left hand, left wrist addition to and back of left handapplication right leg right on each improved forearm clinical 100%.stomach visit Stomach, back of left wrist leg and left elbow improved30-40%. 04 56 M left knee 1 day One none Complete y.o. right treatmentresolution. knee back of right foot 05 46 M left knee 1 day One cocobutter Complete y.o. treatment resolution. 06 Tx M right 1 day One oceansalt Complete at 6 foot treatment water resolution. m.o. right leg leftfoot left leg left buttock 07 33 M right 1 month Applied none Completey.o. ankle serum 1x/ resolution of left arm day symptoms. near Partialelbow resolution of physical appearance of lesions. 08 56 F left 7months Applied HUMIRA ® 80-100% y.o. hand serum 1x/ SORIATANE ®resolution left day light therapy involving all wrist laser treatmentlesions. left forearm left elbow right hand right wrist right elbow heelof left foot heel of right foot bottom of left foot 09 63 M left knee 6months Applied none 90-100% y.o. left serum 1x/ resolution forearm dayinvolving all near lesions. elbow right knee right forearm near elbow 1053 F left 1 day One VASELINE ® Reported y.o. knuckles treatment benefit,left however, pt. elbow was unable to left follow-up due ankle to righttransportation knuckles issues. right elbow 11 60 F left hand 1 day Onetopical 80% y.o. left arm treatment triamcinolone resolution. left footacetonide left 0.1% 2x/day ankle steroid left leg injections rightprednisone hand topical right corticosteroid arm lotion right foot rightankle right leg upper back lower back 12 39 F right elbow 3 weeksApplied artificial 80% resolution of y.o. right arm serum 1x/ tanningsymptoms. 50% right knee day for 3 with UV resolution of right shin wkslights physical left elbow appearance. left forearm near elbow left kneeleft shin stomach 13 48 M facial 3-6 Applied none Complete y.o. monthsserum 1x/ resolution. day 14 37 M upper 1-3 Applied none Complete y.o.torso/neck months serum 1x/ resolution. day

Example 6

One male patient has reported relief of sunburn pain after a singleapplication of the serum prepared in Example 1. The serum was applied tothe sunburnt area in the evening prior to bedtime and the patientreported relief when he awoke in the morning.

While certain preferred and alternative embodiments of the presentinvention have been set forth for purposes of disclosing the invention,modifications to the disclosed embodiments may occur to those who areskilled in the art. Accordingly, the appended claims are intended tocover all embodiments of the invention and modifications thereof whichdo not depart from the spirit and scope of the invention.

All documents, patents and other literature referred to herein areincorporated by reference in their entirety.

The term “comprising” as used in the following claims is an open-endedtransitional term that is intended to include additional elements notspecifically recited in the claims. The term “consisting essentially of”as used in the following claims is a partially closed transitionalphrase and is intended to include the recited elements plus anyunspecified elements that do not materially affect the basic and novelcharacteristics of the claims. For example, an adhesive laminate (theoutermost layer of the applied patch) embossed or printed with indiciawould still be included in the meaning of “consisting essentially of”,even if not specifically recited. The term “consisting of” as used inthe following claims is intended to indicate that the claims arerestricted to the recited elements.

It should be noted that it is envisioned that any feature or elementthat is positively identified in this document may also be specificallyexcluded as a feature or element of an embodiment of the presentinvention.

1. A topical composition comprising: (a) about 40 wt % to about 99 wt %a C₁₀-C₃₀ carboxylic acid cholesterol/lanosterol mixture; (b) about 0.01wt % to about 15 wt % of a penetration enhancer; (c) about 0.1 wt % toabout 10 wt % of a film forming polymeric agent; (d) about 0.005 wt % toabout 40 wt % of a viscosity increasing agent; (e) 0 to about 10 wt % ofan antioxidant; and (f) 0 to about 10 wt % of a preservative.
 2. Thetopical composition of claim 1 wherein the penetration enhancer isselected from the group consisting of oleyl alcohol, lauryl alcohol,isopropyl myristate, oleyl oleate, levulinic acid, glycerol monooleate,methyl laurate, sorbitan monooleate, triacetin, cetyl alcohol, cetyllactate, dimethyl isosorbide, dipropylene glycol, ethyl hexyl lactate,glycolic acid, lauramine oxide, lauryl betaine, lauryl lactate, lauryllaurate, isopropyl pamitate, myristyl alcohol, myristal lactate, octylsalicylate, oleamine oxide, oleic acid, oleyl betaine, salicylic acid,stearyl alcohol, stearyl lactate, triethanolamine triacetate, andcombinations thereof.
 3. The topical composition of claim 1 wherein thefilm forming polymeric agent comprises a water insoluble film formingpolymeric agent.
 4. The topical composition of claim 1 wherein thefilm-forming polymeric agent is selected from the group consisting ofpolyalkenes, oleophilic copolymers of vinylpyrrolidone, acryliccopolymers, polyethylene glycol derivatives, polyolefins, polyurethanes,and mixtures thereof.
 5. The topical composition of claim 1 wherein theviscosity increasing agent is selected from the group consisting ofnatural waxes, synthetic waxes, gelling agents, fumed silicas, clays,hydrogenated vegetable oils, petrolatums and mixtures thereof.
 6. Thetopical composition of claim 1 wherein the carboxylic acidcholesterol/lanosterol mixture comprises about 75 wt % to about 95 wt %of the topical composition.
 7. The topical composition of claim 1wherein the carboxylic acid cholesterol/lanosterol mixture comprisesabout 80 wt % to about 95 wt % of the topical composition.
 8. Thetopical composition of claim 1 wherein the carboxylic acidcholesterol/lanosterol mixture comprises about 60 wt % to about 90 wt %of the topical composition.
 9. The topical composition of claim 1wherein the carboxylic acid cholesterol/lanosterol mixture comprisesabout 60 wt % to about 85 wt % of the topical composition.
 10. Thetopical composition of claim 1 wherein the penetration enhancercomprises a penetration enhancer selected from the group consisting oflauryl laurate, oleic acid or a combination thereof.
 11. The topicalcomposition of claim 1 wherein the film forming polymeric agentcomprises a polyurethane.
 12. The topical composition of claim 1 whereinthe viscosity increasing agent comprises a hydrogenated vegetable oil.13. A topical composition comprising: (a) about 60 wt % to about 99 wt %a C₁₀-C₃₀ carboxylic acid cholesterol/lanosterol mixture; (b) about 0.01wt % to about 15 wt % of a penetration enhancer wherein the penetrationenhancer comprises a penetration enhancer selected from the groupconsisting of lauryl laurate, oleic acid or a combination thereof; (c)about 0.1 wt % to about 10 wt % of a film forming polymeric agentwherein the film forming polymeric agent comprises a polyurethane; (d)about 0.005 wt % to about 40 wt % of a viscosity increasing agentwherein the viscosity increasing agent comprises a hydrogenatedvegetable oil. (e) 0 to about 10 wt % of an antioxidant; and (f) 0 toabout 10 wt % of a preservative.
 14. The topical composition of claim 13wherein the carboxylic acid cholesterol/lanosterol mixture comprisesabout 75 wt % to about 95 wt % of the topical composition.
 15. Thetopical composition of claim 13 wherein the carboxylic acidcholesterol/lanosterol mixture comprises about 80 wt % to about 95 wt %of the topical composition.
 16. The topical composition of claim 13wherein the carboxylic acid cholesterol/lanosterol mixture comprisesabout 60 wt % to about 90 wt % of the topical composition.
 17. Thetopical composition of claim 13 wherein the carboxylic acidcholesterol/lanosterol mixture comprises about 60 wt % to about 85 wt %of the topical composition.
 18. The topical composition of claim 13comprising about 0.5 wt % to about 5 wt % of an antioxidant wherein theantioxidant comprises an antioxidant selected from the group consistingof Vitamin E, tocopherol, tocopherol acetate and mixed tocopherols. 19.The topical composition of claim 13 wherein the topical compositionfurther comprises 0 to about 15 wt % of a vitamin A.
 20. The topicalcomposition of claim 19 wherein the vitamin A comprises tazarotene orvitamin A palmitate.